This program project represents a coordinated and mutually supporting effort to pursue research in structural biology in areas where electron diffraction and electron microscopy play a key, often unique role. Five of the projects within the Program represent applications of the methods of electron crystallography to specific problems in structural biology: these applications cover (A) structural intermediates in the ion-pumping cycle of bacteriorhodopsin, a model for membrane pumps which alternate between inward-facing and outward-facing protein conformation; (B) two-dimensional crystals of myelin basic protein, an essential component of the nerve- myelin crystallization studies of three members of a family of membrane receptors which include the beta-adrenergic conformational changes in tubulin, a target protein for the development of anti-cancer drugs, of which taxol is a prime example. Three additional projects seeks to further develop the instrumentation, experimental methodology and computational methodology used in high-resolution structural studies by electron crystallography. Project F1 will attempt to improve the quality of image data that an be captured with a CD camera; Project F2 will attempt to reduce the amount of specimen charging that occurs when recording high resolution images; and Project F3 will generate a set of molecular structure factors which more accurately account for modifications in the Coulomb shielding of the charge of the atomic nuclei that occurs when single atoms are covalently bonded into molecular structures. Two additional, already funded research projects which use equipment and facilities supported by this Program Project are also included as Associate Member projects. The Administrative Core (Project F) maintains and schedules major equipment, supports computer resources and provides a sense of intellectual community and common identity for all of the participants in the Program Project.